Semaglutide
Also known as: Ozempic · Wegovy · Rybelsus
An FDA-approved GLP-1 receptor agonist that has revolutionized weight management, producing average weight loss of 15-17% of body weight in clinical trials.
Overview
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that has become one of the most transformative medications in the history of weight management. Originally developed for type 2 diabetes (marketed as Ozempic), it was subsequently approved at a higher dose for chronic weight management (as Wegovy). Semaglutide mimics the incretin hormone GLP-1, which is naturally released from the gut after eating. It works through multiple mechanisms: slowing gastric emptying, reducing appetite through hypothalamic signaling, improving insulin sensitivity, and reducing glucagon secretion.
In the landmark STEP clinical trials, semaglutide 2.4 mg weekly produced an average weight loss of 14.9-16.9% of body weight over 68 weeks — results previously achievable only through bariatric surgery. Beyond weight loss, semaglutide has demonstrated cardiovascular benefits, with the SELECT trial showing a 20% reduction in major adverse cardiovascular events. It also shows promise for reducing liver fat in NASH/MAFLD, and emerging research suggests potential benefits for addiction and neurodegeneration.
Mechanism of Action
Agonist of the GLP-1 receptor. Slows gastric emptying, reduces appetite via hypothalamic GLP-1R activation, enhances glucose-dependent insulin secretion, suppresses glucagon release, and may reduce neuroinflammation. The fatty acid side chain enables albumin binding for extended half-life.
Key Benefits
Potential Side Effects
Common Stacks
This peptide is commonly combined with the following compounds for synergistic effects:
Known Interactions
The following interactions have been documented for Semaglutide. Always consult a healthcare professional before combining compounds.
Contraindicated (4)
Both are GLP-1 receptor agonists. Using together doubles the risk of severe GI side effects (nausea, vomiting, pancreatitis) with no additional benefit.
Retatrutide already includes GLP-1 agonism. Adding semaglutide creates dangerous receptor overlap with high risk of severe GI distress and hypoglycemia.
Survodutide is a dual GLP-1/glucagon agonist. Adding semaglutide creates excessive GLP-1 stimulation with high GI side effect risk.
Mazdutide is a dual GLP-1/glucagon agonist. Combining with semaglutide creates dangerous GLP-1 receptor overlap.
Use Caution (2)
MK-677 increases appetite significantly while semaglutide suppresses it. The opposing effects may reduce the efficacy of either compound's primary benefit.
Both suppress appetite through different mechanisms. Combined use may cause excessive appetite suppression, nutritional deficiencies, and cardiovascular strain.
Synergistic (4)
GLP-1 (semaglutide) + amylin analog (cagrilintide) targets two distinct satiety pathways. This combination (CagriSema) is in clinical trials showing superior weight loss.
AOD-9604 targets fat metabolism directly (lipolysis) while semaglutide reduces appetite. Different mechanisms that can complement each other for fat loss.
Both improve metabolic health through different mechanisms. Semaglutide (GLP-1) + Metformin (AMPK) is a well-studied combination for type 2 diabetes and weight management.
BPC-157 may help protect the GI tract from semaglutide's common GI side effects (nausea, gastroparesis) through its gastroprotective properties.
Scientific References
Quick Reference
Typical Dose
0.25-2.4 mg/week (titrated up over 16-20 weeks)
Frequency
Once weekly
Route
Subcutaneous injection (or oral for Rybelsus)
Half-Life
~7 days
Cycle Length
Ongoing (chronic therapy); weight regain common upon discontinuation
FDA Status
FDA approved (Ozempic for T2D; Wegovy for weight management)
Need to calculate dosing?
Use our reconstitution calculator to determine exact syringe measurements.
Open CalculatorThis information is for educational purposes only. Consult a qualified healthcare professional before using any peptide. Dosing information reflects commonly reported protocols and may not be appropriate for everyone.
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